title: Epidermal growth factor and transforming growth factor-alpha induce differential processing of the epidermal growth factor receptor.
abstract: The capacity of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) to induce internalization and degradation of the EGF receptor was compared in NIH-3T3 cells expressing the human EGF receptor. This study was initiated following the observation that TGF-alpha was much less efficient relative to EGF in generating a Mr = 125,000 amino-terminally truncated degradation product from the mature EGF receptor (EGF-dependent generation of this degradation product is described in S.J. Decker, J. Biol. Chem., 264:17641-17644). Pulse-chase experiments revealed that EGF generally stimulated EGF receptor degradation to a greater extent than TGF-alpha. Both ligands induced EGF receptor internalization to similar degrees. However, recovery of [125I]-EGF binding following incubation with EGF or TGF-alpha was much faster for TGF-alpha treated cells. Recovery of [125I]-EGF binding after TGF-alpha treatment did not appear to require protein synthesis. Tyrosine phosphorylation of EGF receptor from cells treated with TGF-alpha decreased more rapidly following removal of TGF-alpha compared to cells treated similarly with EGF. These data suggest that EGF routes the EGF receptor directly to a degradative pathway, whereas TGF-alpha allows receptor recycling prior to degradation, and that tyrosine phosphorylation could play a role in this differential receptor processing.
authors.affiliation: Rockefeller University, New York, NY 10021.
authors.forename: S J
authors.initials: SJ
authors.lastname: Decker
mesh_terms: D000818:Animals; D002451:Cell Compartmentation; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D014162:Transfection; D015291:Transforming Growth Factors / Q000494:pharmacology*
chemical_list: D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors